A study aiming at evaluating the affect of a new drug serelaxin on the capacity of work of the left chamber of the heart and its impact on the outcome in patients with acute heart failure.

• Conditions: Acute Heart Failure; MedDRA version: 16.1Level: LLTClassification code 10000803Term: Acute heart failureSystem Organ Class: 100000004849; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2013-005054-30-IT
• Lead Sponsor: Ospedale San Raffaele s.r.l.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-03-14
• Last Update Posted: 23 March 2015

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Dyspnea at rest or with minimal exertion
Pulmonary congestion on chest radiograph
Able to start serelaxin infusion within 16 hours from presentation to the hospital
Received IV furosemide of at least 40 mg (or equivalent) at any time between admission to emergency services (either ambulance or hospital, including the ED) and the start of screening for the study.
Impaired renal function defined as an estimated glomerular filtration rate (eGFR) on admission between 30-75 mL/min/1•73 m2, calculated using the simplified Modification of Diet in Renal Disease (sMDRD) equation.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 18
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 18

Exclusion Criteria

Dyspnoea primarily due to non-cardiac causes
Women of child bearing potential or pregnant or nursing (lactating) women
Temperature >38.5°C (oral or equivalent) or sepsis or active infection requiring IV anti-microbial treatment
Current (within 2 hours prior to screening) or planned treatment with any IV vasoactive therapies, including vasodilators, positive inotropic agents and vasopressors, or mechanical support, with the exception of IV furosemide (or equivalent) or IV nitrates = 0.1mg/kg if the patient has a systolic BP >150 mmHg at screening
Significant left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy or severe aortic stenosis (i.e., aortic valve area <1.0 cm2 or mean gradient >50 mmHg on prior or current echocardiogram) and severe mitral stenosis
Known hepatic impairment, or AST or ALT >3 times Upper Limit of Normal of unknown source
Known presence of active or recurrent bacterial, fungal or viral infection at the time of enrollment, e.g. evidence of Human Immunodeficiency Virus (HIV) infection, Hepatitis B and Hepatitis C infections (based on history and/or clinical findings, including laboratory results obtained during screening period, known significant pulmonary disease.
Shock regardless of aetiology
AHF caused by significant arrhythmias, acute myocarditis or hypertrophic obstructive, restrictive, or constrictive cardiomyopathy
Clinical evidence of Acute Coronary Syndrome currently or diagnosed within 30 days prior to enrolment. (Note that the diagnosis of acute coronary syndrome is a clinical diagnosis and that the sole presence of elevated troponin concentrations is not sufficient for a diagnosis of acute coronary syndrome, given that troponin concentrations may be significantly increased in the setting of AHF)
Troponin =3 times the level indicative of myocardial infarction
Known hypersensitivity to Serelaxin or similar substances or to any of the excipients
Pacemaker or ICD.
Implanted ferromagnetic cerebrovascular clips.
Claustrophobia.
Involved in other research studies

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Demonstration of a significant reduction in indexed left ventricular end systolic volume (LVESVi) assessed by cardiac magnetic resonance (CMR) in the serelaxin group compared to controls at 6 months follow up.;Secondary Objective: Changes in LVESVi, assessed by echo, between baseline and 6 month in the serelaxin group compared to controls. <br>- Correlation between changes in echocardiographic parameters of cardiac function and cardiac, renal and hepatic biomarkers.<br>- Changes in late gadolinium enhancement at CMR in the two groups between baseline and 6 months. <br>- Comparison of the NYHA functional class at 6 months between the Serelaxin group and controls. <br>;Primary end point(s): The primary endpoint of the study is the demonstration of a significant reduction in indexed left ventricular end systolic volume (LVESVi) assessed by cardiac magnetic resonance (CMR) in the serelaxin group compared to controls at 6 months follow up.;Timepoint(s) of evaluation of this end point: 6 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Changes in LVESVi, assessed by echo, between baseline and 6 month in the serelaxin group compared to controls. <br>- Correlation between changes in echocardiographic parameters of cardiac function assessed at screening (visit 0), 24 hour, 48 hours, day 4 and at 1, 2, 6 months and cardiac, renal and hepatic biomarkers assessed at baseline, 24 hour, 48 hours, day 4 and at 6 months.<br>- Changes in late gadolinium enhancement at CMR in the two groups between baseline and 6 months. <br>- Comparison of the NYHA functional class at 6 month between the Serelaxin group and controls.<br>;Timepoint(s) of evaluation of this end point: Baseline, 24 hour, 48 hours, day 4 and at 6 months